Back to Search
Start Over
The intramembrane protease SPPL2c promotes male germ cell development by cleaving phospholamban
- Source :
- EMBO reports 20(3), e46449 (2019). doi:10.15252/embr.201846449
- Publication Year :
- 2019
-
Abstract
- Signal peptide peptidase (SPP) and the four homologous SPP‐like (SPPL) proteases constitute a family of intramembrane aspartyl proteases with selectivity for type II‐oriented transmembrane segments. Here, we analyse the physiological function of the orphan protease SPPL2c, previously considered to represent a non‐expressed pseudogene. We demonstrate proteolytic activity of SPPL2c towards selected tail‐anchored proteins. Despite shared ER localisation, SPPL2c and SPP exhibit distinct, though partially overlapping substrate spectra and inhibitory profiles, and are organised in different high molecular weight complexes. Interestingly, SPPL2c is specifically expressed in murine and human testis where it is primarily localised in spermatids. In mice, SPPL2c deficiency leads to a partial loss of elongated spermatids and reduced motility of mature spermatozoa, but preserved fertility. However, matings of male and female SPPL2c −/− mice exhibit reduced litter sizes. Using proteomics we identify the sarco/endoplasmic reticulum Ca 2+ ‐ATPase (SERCA2)‐regulating protein phospholamban (PLN) as a physiological SPPL2c substrate. Accumulation of PLN correlates with a decrease in intracellular Ca 2+ levels in elongated spermatids that likely contribute to the compromised male germ cell differentiation and function of SPPL2c −/− mice.
- Subjects :
- Male
medicine.medical_treatment
Medizin
Biochemistry
Substrate Specificity
Mice
0302 clinical medicine
metabolism [Endoplasmic Reticulum]
Homeostasis
metabolism [Calcium]
metabolism [Spermatids]
0303 health sciences
biology
Chemistry
Articles
metabolism [Aspartic Acid Endopeptidases]
Transmembrane protein
Cell biology
Phospholamban
medicine.anatomical_structure
Organ Specificity
Female
Signal peptide peptidase
Germ cell
Proteases
endocrine system
metabolism [Germ Cells]
Intramembrane protease
enzymology [Testis]
03 medical and health sciences
ddc:570
Genetics
medicine
Animals
Humans
chemistry [Membrane Proteins]
Amino Acid Sequence
ddc:610
Molecular Biology
030304 developmental biology
chemistry [Aspartic Acid Endopeptidases]
Protease
enzymology [Cell Membrane]
Endoplasmic reticulum
metabolism [Calcium-Binding Proteins]
HEK293 Cells
biology.protein
030217 neurology & neurosurgery
metabolism [Membrane Proteins]
HeLa Cells
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- EMBO reports 20(3), e46449 (2019). doi:10.15252/embr.201846449
- Accession number :
- edsair.doi.dedup.....1418b4ad477efe0f728a4ddd7233c8b6